Safety and Efficacy Trial of a Dapivirine Vaginal Matrix Ring in Healthy HIV-Negative Women

NCT01539226 | Completed Results DMC

• 1 other identifier: IPM 027
• Study Type: interventional
• Target: 1,959
• Locations: 2 countries
• Sites: 7

Brief Summary

This is a double-blind, randomised, placebo-controlled study to assess the safety and efficacy of a silicone elastomer vaginal matrix ring.

Conditions

HIV Infections

Keywords

HIV Infections; Anti-HIV agents; HIV-1

Outcome Measures

Primary Outcomes (2)

• HIV-1 Seroconversion According to Comprehensive HIV Testing Algorithm.

  HIV-1 seroconversion measured by rapid and specialised laboratory testing according to the comprehensive HIV testing algorithm.

  24 months

• All Adverse Events

  Self-reports, physical examination, gynaecological assessments, including pelvic/speculum examination, laboratory tests and other indicated investigations. All AEs will be reported, regardless of grade or relatedness.

  24 months

Secondary Outcomes (6)

• The Incidence Rate of HIV-2 Seroconversion.

  24 months

• The Incidence of Curable STIs

  24 months

• Percentage of Participants With Pregnancy in Each Trial Arm Over the IP Use Period;

  24 months

• The Percentage of Women Who Report Adherence to the Use of the Vaginal Ring Inserted Once Every 4 Weeks Over the Trial Period;

  24 months

• The Percentage of Women Who Report the Use of the Vaginal Ring as Acceptable;

  24 months

Study Arms (2)

Placebo Vaginal Ring

PLACEBO COMPARATOR

Vaginal Ring containing 0.0 mg Dapivirine

Combination Product: Placebo Vaginal Ring

Dapivirine Vaginal Ring

EXPERIMENTAL

Vaginal Ring containing 25mg of Dapivirine

Combination Product: Dapivirine Vaginal Ring, 25 mg

Interventions

Placebo Vaginal Ring COMBINATION_PRODUCT

Dapivirine Vaginal Ring containing 0.0 mg of dapivirine

Placebo Vaginal Ring

Dapivirine Vaginal Ring, 25 mg COMBINATION_PRODUCT

Dapivirine Vaginal Ring containing 25 mg of dapivirine

Dapivirine Vaginal Ring

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Women \> 18 and \< 45 years of age, at screening, who can provide informed consent;
• Available for all visits and consent to follow all procedures scheduled for the trial;
• Self-reported sexually active (defined as an average of at least one penetrative penile-vaginal coital act per month for the last 3 months prior to screening);
• HIV-negative as determined by the HIV algorithm applied at screening and enrolment;
• On a stable form of contraception as defined within section 5.4 and willing to continue on stable contraception for the duration of the clinical trial, unless post-menopausal or surgically sterilised;
• Asymptomatic for genital infections at the time of enrolment (if a woman is diagnosed with any clinically significant curable STI, she must have initiated treatment at least 1 week prior to enrolment and have completed the full course of treatment);
• Willing to provide adequate locator information for trial retention purposes and be reachable per local standard procedures (e.g., by home visit or telephone; or via family or close neighbour contacts); confidentiality to be maintained;
• Willing to refrain from participation in another research trial using drugs, vaccines, medical devices, microbicides or oral pre-exposure prophylaxis investigational drugs for the duration of the IPM 027 trial.

You may not qualify if:

• Currently pregnant or last pregnancy within 3 months prior to screening or intends to become pregnant during trial participation;
• Currently breast-feeding;
• Non-therapeutic injection drug use in the 12 months prior to screening;
• Participated in another research trial using drugs, medical devices, microbicides or oral pre-exposure prophylaxis agents within 60 days prior to screening;
• Previously participated or currently participating in any HIV vaccine trial;
• Untreated, clinically significant urogenital infections , e.g., urinary tract, or other sexually transmitted infections, or other gynaecological symptoms within 1 week prior to enrolment;
• Has a Grade 2 or higher pelvic examination finding, according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events; Addendum 1 Female Genital Grading Table for Use in Microbicide Studies;
• History of significant urogenital or uterine prolapse, undiagnosed vaginal bleeding, diagnosed chronic and/or recurrent vulvovaginal candidiasis, urethral obstruction, incontinence or urge incontinence;
• Any gynaecological surgery within 90 days prior to screening;
• Any Grade 1 or higher baseline aspartate aminotransferase (AST), alanine transaminase (ALT), or platelet count, and any Grade 2 or higher baseline haematology, chemistry or urinalysis laboratory value according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events;
• Any history of anaphylaxis or severe allergy resulting in angioedema; or a history of sensitivity/allergy to latex or a silicone elastomer;
• Any history of diabetes mellitus and chronic use of oral corticosteroid therapy; and any uncontrolled serious chronic or progressive disease;
• Cervical cytology at screening that requires cryotherapy, biopsy or treatment (other than for infection). Women with Grade 1 cervical cytology findings can be enrolled upon completion of the initial phase of evaluation if no current treatment is indicated (based on local standard of care for management of abnormal cervical cytology);
• Any condition(s) that, in the opinion of the investigator, might put the participant at risk, or interfere with the trial objectives or the participant's adherence to trial requirements.

Sponsors & Collaborators

• International Partnership for Microbicides, Inc.: lead

Study Sites (7)

Qhakaza Mbokodo

Ladysmith, KwaZulu-Natal, South Africa

Location

Prevention of HIV / AIDS (PHIVA) Project

Pinetown, KwaZulu-Natal, 3610, South Africa

Location

Ndlovu Medical Centre

Elandsdoorn, Limpopo, 0485, South Africa

Location

Madibeng Centre for Research (MCR)

Brits, 0250, South Africa

Location

Desmond Tutu HIV Foundation, Guinea Fowl Road, Sunnydale, Fish Hoek

Cape Town, 7975, South Africa

Location

Maternal, Adolescent and Child Health (MatCH)

Plessislaer, 3216, South Africa

Location

MRC/UVRI Uganda Research Unit on AIDS, Plot 51-59, Nakiwogo Road, PO BOX 49

Masaka, Uganda

Location

Related Publications (5)

• Kusemererwa S, Ruzagira E, Onyango M, Kabarambi A, Abaasa A. Associations between intravaginal practices and incidence of sexually transmitted infections and bacterial vaginosis among women enrolled in the dapivirine vaginal ring trial (The Ring Study) in southwestern Uganda: a retrospective secondary analysis. BMJ Open. 2024 Apr 8;14(4):e079497. doi: 10.1136/bmjopen-2023-079497.

  PMID: 38589266 DERIVED

• Steytler J, Craig C, van der Ryst E, Van Baelen B, Nuttall J, van Niekerk N, Mellors J, Parikh U, Wallis C; Ring Study and the DREAM Trial Study Teams. Characterization of Viruses in Phase 3 and Phase 3b Trials (the Ring Study and the Dapivirine Ring Extended Access and Monitoring Trial) of the Dapivirine Vaginal Ring for Human Immunodeficiency Virus Type 1 Infection Risk Reduction. Clin Infect Dis. 2023 Mar 21;76(6):996-1002. doi: 10.1093/cid/ciac875.

  PMID: 36345569 DERIVED

• Kusemererwa S, Abaasa A, Kabarambi A, Onyango M, Mugisha JO. Assessment of risk compensation following use of the dapivirine vaginal ring in southwestern Uganda. Sex Transm Infect. 2022 Feb;98(1):32-37. doi: 10.1136/sextrans-2020-054718. Epub 2021 Feb 4.

  PMID: 33542153 DERIVED

• Kusemererwa S, Abaasa A, Onyango M, Nel AM, Isaacs M, Asiki G. Contraceptive Preference Among Women at Risk of HIV Acquisition in a Preparatory Screening Study for a Phase III Microbicide Trial in South Western Uganda. AIDS Behav. 2018 Jul;22(Suppl 1):131-138. doi: 10.1007/s10461-018-2177-3.

  PMID: 29855975 DERIVED

• Nel A, van Niekerk N, Kapiga S, Bekker LG, Gama C, Gill K, Kamali A, Kotze P, Louw C, Mabude Z, Miti N, Kusemererwa S, Tempelman H, Carstens H, Devlin B, Isaacs M, Malherbe M, Mans W, Nuttall J, Russell M, Ntshele S, Smit M, Solai L, Spence P, Steytler J, Windle K, Borremans M, Resseler S, Van Roey J, Parys W, Vangeneugden T, Van Baelen B, Rosenberg Z; Ring Study Team. Safety and Efficacy of a Dapivirine Vaginal Ring for HIV Prevention in Women. N Engl J Med. 2016 Dec 1;375(22):2133-2143. doi: 10.1056/NEJMoa1602046.

  PMID: 27959766 DERIVED

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Limitations and Caveats

Dapivirine residual levels in used rings and dapivirine plasma concentrations are two objective measures of adherence to DVR ring use; however, they were found to be an imperfect measure of adherence as they cannot distinguish different patterns of use during the month. In addition, self-reported adherence based on the adherence questionnaires was also considered to have limitations.

Results Point of Contact

• Title: Dr John Steytler
• Organization: International Partnership for Microbicides

jsteytler@ipmglobal.org

Study Officials

• Annalene Nel

  Beijing Immupeutics Medicine Technology Limited

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2012
• First Posted: February 27, 2012
• Study Start: March 27, 2012
• Primary Completion: December 13, 2016
• Study Completion: December 13, 2016
• Last Updated: October 19, 2022
• Results First Posted: October 19, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

UG (1); ZA (6)